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Chronic–Progressive Dopaminergic Deficiency Does Not Induce Midbrain Neurogenesis

Authors :
Sigrid C. Schwarz
Mareike Fauser
Johannes Schwarz
Francisco Pan-Montojo
Andreas Hermann
Philipp J. Kahle
Christian Richter
Alexander Storch
Source :
Cells, Vol 10, Iss 775, p 775 (2021), Cells 10(4), 775-(2021). doi:10.3390/cells10040775, Cells, Volume 10, Issue 4
Publication Year :
2021
Publisher :
MDPI AG, 2021.

Abstract

Background: Consecutive adult neurogenesis is a well-known phenomenon in the ventricular–subventricular zone of the lateral wall of the lateral ventricles (V–SVZ) and has been controversially discussed in so-called “non-neurogenic” brain areas such as the periventricular regions (PVRs) of the aqueduct and the fourth ventricle. Dopamine is a known modulator of adult neural stem cell (aNSC) proliferation and dopaminergic neurogenesis in the olfactory bulb, though a possible interplay between local dopaminergic neurodegeneration and induction of aNSC proliferation in mid/hindbrain PVRs is currently enigmatic. Objective/Hypothesis: To analyze the influence of chronic–progressive dopaminergic neurodegeneration on both consecutive adult neurogenesis in the PVRs of the V–SVZ and mid/hindbrain aNSCs in two mechanistically different transgenic animal models of Parkinson´s disease (PD). Methods: We used Thy1-m[A30P]h α synuclein mice and Leu9′Ser hypersensitive α4* nAChR mice to assess the influence of midbrain dopaminergic neuronal loss on neurogenic activity in the PVRs of the V–SVZ, the aqueduct and the fourth ventricle. Results: In both animal models, overall proliferative activity in the V–SVZ was not altered, though the proportion of B2/activated B1 cells on all proliferating cells was reduced in the V–SVZ in Leu9′Ser hypersensitive α4* nAChR mice. Putative aNSCs in the mid/hindbrain PVRs are known to be quiescent in vivo in healthy controls, and dopaminergic deficiency did not induce proliferative activity in these regions in both disease models. Conclusions: Our data do not support an activation of endogenous aNSCs in mid/hindbrain PVRs after local dopaminergic neurodegeneration. Spontaneous endogenous regeneration of dopaminergic cell loss through resident aNSCs is therefore unlikely.

Details

Language :
English
ISSN :
20734409
Volume :
10
Issue :
775
Database :
OpenAIRE
Journal :
Cells
Accession number :
edsair.doi.dedup.....6cf572df2e281fae610d33b0527451be
Full Text :
https://doi.org/10.3390/cells10040775